Cortisone Reductase Deficiency 1 (CORTRD1)

Categories: Endocrine diseases, Genetic diseases, Metabolic diseases
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Aliases & Classifications for Cortisone Reductase Deficiency 1

MalaCards integrated aliases for Cortisone Reductase Deficiency 1:

Name: Cortisone Reductase Deficiency 1 57 11 73 28 5 71
Cortrd1 57 11 73
Cortisone Reductase Deficiency, Type 1 38



Autosomal recessive 57


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Disease Ontology 11 DOID:0090141
OMIM® 57 604931
OMIM Phenotypic Series 57 PS604931
MeSH 43 D008661
NCIt 49 C131849
MedGen 40 C3551716
UMLS 71 C3551716

Summaries for Cortisone Reductase Deficiency 1

OMIM®: 57 Cortisone reductase deficiency (CRD) results from a failure to regenerate the active glucocorticoid cortisol from cortisone via the enzyme 11-beta-hydroxysteroid dehydrogenase (HSD11B1; 600713). The oxoreductase activity of 11-beta-HSD requires the NADPH-regenerating enzyme hexose-6-phosphate dehydrogenase (H6PD; 138090) within the endoplasmic reticulum. Lack of cortisol regeneration stimulates ACTH-mediated adrenal hyperandrogenism, with males manifesting in early life with precocious pseudopuberty and females presenting in midlife with hirsutism, oligomenorrhea, and infertility. Biochemically, CRD is diagnosed through the assessment of urinary cortisol and cortisone metabolites and consists of measuring the tetrahydrocortisol (THF) plus 5-alpha-THF/tetrahydrocortisone (THE) ratio, which in CRD patients is typically less than 0.1 (reference range, 0.7 to 1.2) (summary by Lavery et al., 2008). (604931) (Updated 08-Dec-2022)

MalaCards based summary: Cortisone Reductase Deficiency 1, also known as cortrd1, is related to cortisone reductase deficiency 2. An important gene associated with Cortisone Reductase Deficiency 1 is H6PD (Hexose-6-Phosphate Dehydrogenase/Glucose 1-Dehydrogenase). Affiliated tissues include pituitary, liver and brain, and related phenotypes are precocious puberty and acne

Disease Ontology: 11 A cortisone reductase deficiency that is characterized by failure to regenerate cortisol via the enzyme 11-beta-hydroxysteroid dehydrogenase which requires NADPH regeneration by hexose-6-phosphate dehydrogenase, resulting in ACTH-mediated adrenal hyperandrogenism. It has material basis in autosomal recessive inheritance of homozygous or compound heterozygous mutation in the hexose-6-phosphate dehydrogenase gene (H6PD) on chromosome 1p36.

UniProtKB/Swiss-Prot: 73 An autosomal recessive error of cortisone metabolism characterized by a failure to regenerate cortisol from cortisone, resulting in increased cortisol clearance, activation of the hypothalamic-pituitary axis and ACTH-mediated adrenal androgen excess. Clinical features include hyperandrogenism resulting in hirsutism, oligo-amenorrhea, and infertility in females and premature pseudopuberty in males.

Related Diseases for Cortisone Reductase Deficiency 1

Diseases related to Cortisone Reductase Deficiency 1 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 cortisone reductase deficiency 2 11.0

Symptoms & Phenotypes for Cortisone Reductase Deficiency 1

Human phenotypes related to Cortisone Reductase Deficiency 1:

30 (show all 7)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 precocious puberty 30 Very rare (1%) HP:0000826
2 acne 30 Very rare (1%) HP:0001061
3 alopecia 30 Very rare (1%) HP:0001596
4 infertility 30 Very rare (1%) HP:0000789
5 hirsutism 30 Very rare (1%) HP:0001007
6 oligomenorrhea 30 Very rare (1%) HP:0000876
7 obesity 30 HP:0001513

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Skin Nails Hair Skin:

Genitourinary Internal Genitalia Female:

Endocrine Features:
delayed conversion of oral cortisone acetate to plasma cortisol
low tetrahydrocortisol (thf) plus 5-alpha-thf/tetrahydrocortisone (the) ratio
low urinary cortols-to-cortolone ratio
low to normal level of cortisol metabolites
Growth Weight:
central fat distribution

Skin Nails Hair Hair:
androgenic alopecia (in some patients)

Genitourinary External Genitalia Male:
precocious puberty, gonadotropin-independent

Clinical features from OMIM®:

604931 (Updated 08-Dec-2022)

Drugs & Therapeutics for Cortisone Reductase Deficiency 1

Search Clinical Trials, NIH Clinical Center for Cortisone Reductase Deficiency 1

Genetic Tests for Cortisone Reductase Deficiency 1

Genetic tests related to Cortisone Reductase Deficiency 1:

# Genetic test Affiliating Genes
1 Cortisone Reductase Deficiency 1 28 H6PD

Anatomical Context for Cortisone Reductase Deficiency 1

Organs/tissues related to Cortisone Reductase Deficiency 1:

MalaCards : Pituitary, Liver, Brain, Ovary
ODiseA: Brain, Liver, Adipose-Subcutaneous, Adipose, Adipose-Visceral

Publications for Cortisone Reductase Deficiency 1

Articles related to Cortisone Reductase Deficiency 1:

# Title Authors PMID Year
Steroid biomarkers and genetic studies reveal inactivating mutations in hexose-6-phosphate dehydrogenase in patients with cortisone reductase deficiency. 57 5
18628520 2008
Mutations in the genes encoding 11beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase interact to cause cortisone reductase deficiency. 57 5
12858176 2003
Apparent cortisone reductase deficiency: a rare cause of hyperandrogenemia and hypercortisolism. 57 5
11150889 2000
Apparent cortisone reductase deficiency: a functional defect in 11beta-hydroxysteroid dehydrogenase type 1. 57 5
10522997 1999
Lack of Association of the 11beta-hydroxysteroid dehydrogenase type 1 gene 83,557insA and hexose-6-phosphate dehydrogenase gene R453Q polymorphisms with body composition, adrenal androgen production, blood pressure, glucose metabolism, and dementia. 57
17062770 2007
Variants implicated in cortisone reductase deficiency do not contribute to susceptibility to common forms of polycystic ovary syndrome. 57
16817821 2006
Genotypes at 11beta-hydroxysteroid dehydrogenase type 11B1 and hexose-6-phosphate dehydrogenase loci are not risk factors for apparent cortisone reductase deficiency in a large population-based sample. 57
16091483 2005
Apparent cortisone reductase deficiency: a unique form of hypercortisolism. 57
8923828 1996
Defects in the HSD11 gene encoding 11 beta-hydroxysteroid dehydrogenase are not found in patients with apparent mineralocorticoid excess or 11-oxoreductase deficiency. 57
8370690 1993
A new defect in the peripheral conversion of cortisone to cortisol. 57
3990293 1985

Variations for Cortisone Reductase Deficiency 1

ClinVar genetic disease variations for Cortisone Reductase Deficiency 1:

# Gene Name Type Significance ClinVarId dbSNP ID Position
1 H6PD NM_004285.4(H6PD):c.960G>A (p.Val320=) SNV Pathogenic
31584 rs398122816 GRCh37: 1:9322332-9322332
GRCh38: 1:9262273-9262273
2 H6PD NM_004285.4(H6PD):c.1076G>A (p.Gly359Asp) SNV Pathogenic
31585 rs387907167 GRCh37: 1:9323628-9323628
GRCh38: 1:9263569-9263569
3 H6PD NM_004285.4(H6PD):c.948C>G (p.Tyr316Ter) SNV Pathogenic
31586 rs398122817 GRCh37: 1:9322320-9322320
GRCh38: 1:9262261-9262261
4 H6PD NM_004285.4(H6PD):c.325del (p.Arg109fs) DEL Pathogenic
31587 rs398122818 GRCh37: 1:9305317-9305317
GRCh38: 1:9245258-9245258
5 H6PD NM_004285.4(H6PD):c.1860_1861insACAGGTGGTTGACCTGTGGCCGGGTCTGA (p.Glu621delinsThrGlyGlyTer) INSERT Pathogenic
16130 rs606231222 GRCh37: 1:9324412-9324413
GRCh38: 1:9264353-9264354
6 H6PD NM_004285.4(H6PD):c.1109G>A (p.Arg370Gln) SNV Uncertain Significance
1030761 rs182877860 GRCh37: 1:9323661-9323661
GRCh38: 1:9263602-9263602
7 H6PD NM_004285.4(H6PD):c.1358G>A (p.Arg453Gln) SNV Uncertain Significance
16131 rs6688832 GRCh37: 1:9323910-9323910
GRCh38: 1:9263851-9263851
8 H6PD NM_004285.4(H6PD):c.745+88T>A SNV Benign
191261 rs12032814 GRCh37: 1:9307230-9307230
GRCh38: 1:9247171-9247171

UniProtKB/Swiss-Prot genetic disease variations for Cortisone Reductase Deficiency 1:

# Symbol AA change Variation ID SNP ID
1 H6PD p.Pro146Leu VAR_069193
2 H6PD p.Gly359Asp VAR_083055 rs387907167

Expression for Cortisone Reductase Deficiency 1

Search GEO for disease gene expression data for Cortisone Reductase Deficiency 1.

Pathways for Cortisone Reductase Deficiency 1

GO Terms for Cortisone Reductase Deficiency 1

Sources for Cortisone Reductase Deficiency 1

8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
27 GO
28 GTR
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
36 LifeMap
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
70 Tocris
72 UMLS via Orphanet
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